Smoking Behavior and Major Cardiovascular and Limb Events in Patients With Peripheral Artery Disease

Importance: Smoking is the strongest modifiable risk factor for peripheral arterial disease (PAD), yet evidence on how postdiagnosis smoking behavior changes affect clinical outcomes remains limited. Objective: To evaluate the association among smoking cessation, reduction, and continuation after PAD diagnosis and subsequent cardiovascular and limb-specific outcomes. Design, Setting, and Participants: This nationwide, population-based, retrospective cohort study assessed adults 40 years or older newly diagnosed with PAD from January 1, 2011, to December 31, 2018, with follow-up through 2021, who reported active smoking before diagnosis and completed health examinations before and after diagnosis. Data were from the Korean National Health Insurance Service-National Health Information Database. Data analysis was conducted from December 2023 to November 2025. Exposures: Postdiagnosis smoking behavior, classified as quitters (complete cessation), reducers (≥20% decrease in daily cigarette consumption), or maintainers (<20% decrease or any increase in consumption [reference group]). Main Outcomes and Measures: Main outcomes were major adverse cardiovascular and cerebrovascular events (MACCEs), including all-cause death, myocardial infarction, coronary revascularization, and ischemic stroke, and major adverse limb events (MALEs), including limb revascularization or major amputation. Inverse probability of treatment-weighted hazard ratios (HRs) were estimated using Cox proportional hazards regression models for MACCEs and Fine-Gray competing risk models for MALEs. Results: Among 189 545 active smokers with incident PAD (mean [SD] age, 54.2 [11.8] years; 167 659 [88.5%] male), 38 952 (20.6%) quit smoking, 38 709 (20.4%) reduced consumption, and 111 884 (59.0%) maintained smoking. Compared with maintainers, quitters had significantly lower risks of MACCEs (17.8 vs 20.2 per 1000 person-years; HR, 0.88; 95% CI, 0.84-0.91) and MALEs (1.4 vs 1.8 per 1000 person-years; HR, 0.83; 95% CI, 0.73-0.94). Reducers showed no significant difference in MACCEs (HR, 1.00; 95% CI, 0.96-1.04) or MALEs (HR, 0.92; 95% CI, 0.81-1.04). Dose-response analysis showed risk reduction only with near-complete cessation. Findings were consistent across subgroups, with the largest reductions observed for myocardial infarction. Conclusions and Relevance: In this cohort study of 189 545 active smokers with newly diagnosed PAD, complete smoking cessation was associated with lower risks of both cardiovascular and limb-specific adverse events, whereas partial smoking reduction showed no significant benefit. These findings support complete cessation as the primary therapeutic target in patients with PAD.